tbuckley/cabot-search huggingface dataset:
Editor's Choice – John Ingram – November 2023
Journal: British Journal of Dermatology (2023)

Tumour and immune microenvironment differences between clinical subsets of cutaneous squamous cell carcinomaIn this study the authors characterized the genomic, transcriptomic and immunohistochemical profiles of 211 cutaneous squamous cell carcinomas (cSCCs), including 37 cSCCs from immunocompromised patients.cSCCs from immunocompromised patients were characterized by a lack of B cells in the peritumoral stroma, compared with immunocompetent patients.An abundance of a memory B-cell-like population in the peritumoral stroma was associated with a better prognosis in all patients and CD20, a pan-B cell marker, was found to be prognostic, even in immunocompetent patients.No differences in genetic variants, tumour mutational burden or mutational signatures were observed between cSCCs from immunocompetent and immunocompromised patients.The authors concluded that differences in survival between cSCCs from immunocompromised patients and immunocompetent patients are likely to be associated with differential host immune response.They also found that non-head and neck cSCCs with poorer responses to immune checkpoint inhibition had lower tumour mutational burden and exhibited upregulation of the epithelial-mesenchymal transition programme than head and neck cSCC.
Time to treat the climate and nature crisis as one indivisible global health emergency
Authors: Kamran Abbasi, Parveen Ali, Virginia Barbour, Thomas Benfield, Kirsten Bibbins-Domingo, Stephen Hancocks, Richard Horton, Laurie Laybourn-Langton, Robert Mash, Peush Sahni, Wadeia Mohammad Sharief, Paul Yonga, Chris Zielinski
Journal: The Lancet (2023)
PhylteR: Efficient Identification of Outlier Sequences in Phylogenomic Datasets
Authors: Aurore Comte, Théo Tricou, Eric Tannier, Julien Joseph, Aurélie Siberchicot, Simon Penel, Rémi Allio, Frédéric Delsuc, Stéphane Dray, Damien M de Vienne
Journal: Molecular Biology and Evolution (2023)

In phylogenomics, incongruences between gene trees, resulting from both artifactual and biological reasons, can decrease the signal-to-noise ratio and complicate species tree inference. The amount of data handled today in classical phylogenomic analyses precludes manual error detection and removal. However, a simple and efficient way to automate the identification of outliers from a collection of gene trees is still missing. Here, we present PhylteR, a method that allows rapid and accurate detection of outlier sequences in phylogenomic datasets, i.e. species from individual gene trees that do not follow the general trend. PhylteR relies on DISTATIS, an extension of multidimensional scaling to 3 dimensions to compare multiple distance matrices at once. In PhylteR, these distance matrices extracted from individual gene phylogenies represent evolutionary distances between species according to each gene. On simulated datasets, we show that PhylteR identifies outliers with more sensitivity and precision than a comparable existing method. We also show that PhylteR is not sensitive to ILS-induced incongruences, which is a desirable feature. On a biological dataset of 14,463 genes for 53 species previously assembled for Carnivora phylogenomics, we show (i) that PhylteR identifies as outliers sequences that can be considered as such by other means, and (ii) that the removal of these sequences improves the concordance between the gene trees and the species tree. Thanks to the generation of numerous graphical outputs, PhylteR also allows for the rapid and easy visual characterization of the dataset at hand, thus aiding in the precise identification of errors. PhylteR is distributed as an R package on CRAN and as containerized versions (docker and singularity).
Case 33-2023: An 86-Year-Old Man with Shortness of Breath
Authors: Sushil Allen Luis, Ryan Chung, Ada C. Stefanescu Schmidt, Jeffrey W. Clark, Daniel S. Pearson
Journal: New England Journal of Medicine (2023)

An 86-year-old man was admitted to the hospital because of shortness of breath and hypoxemia. Echocardiography revealed severe tricuspid regurgitation and a patent foramen ovale. A diagnosis was made.
CD19 occupancy with tafasitamab increases therapeutic index of CART19 cell therapy and diminishes severity of CRS
Authors: R. Leo Sakemura, Claudia Manriquez Roman, Paulina Horvei, Elizabeth L. Siegler, James H. Girsch, Olivia L. Sirpilla, Carli M. Stewart, Kun Yun, Ismail Can, Ekene J. Ogbodo, Mohamad M. Adada, Evandro D. Bezerra, Lionel Aurelien Kankeu Fonkoua, Mehrdad Hefazi, Michael W. Ruff, Brooke L. Kimball, Long K. Mai, Truc N. Huynh, Wendy K. Nevala, Kristina Ilieva, Christian Augsberger, Maria Patra-Kneuer, Jürgen Schanzer, Jan Endell, Christina Heitmüller, Stefan Steidl, Sameer A. Parikh, Wei Ding, Neil E. Kay, Grzegorz S. Nowakowski, Saad S. Kenderian
Journal: Blood (2023)

In the development of various strategies of anti-CD19 immunotherapy for the treatment of B-cell malignancies, it remains unclear whether CD19 monoclonal antibody therapy impairs subsequent CD19-targeted chimeric antigen receptor T-cell (CART19) therapy. We evaluated the potential interference between the CD19-targeting monoclonal antibody tafasitamab and CART19 treatment in preclinical models. Concomitant treatment with tafasitamab and CART19 showed major CD19 binding competition, which led to CART19 functional impairment. However, when CD19+ cell lines were pretreated with tafasitamab overnight and the unbound antibody was subsequently removed from the culture, CART19 function was not affected. In preclinical in vivo models, tafasitamab pretreatment demonstrated reduced incidence and severity of cytokine release syndrome and exhibited superior antitumor effects and overall survival compared with CART19 alone. This was associated with transient CD19 occupancy with tafasitamab, which in turn resulted in the inhibition of CART19 overactivation, leading to diminished CAR T apoptosis and pyroptosis of tumor cells.
Strategies for Data Ethics Governance: Elevating Patient and Community Perspectives
Authors: Austin M. Stroud, Journey L. Wise, Susan H. Curtis, Michelle L. McGowan
Journal: The American Journal of Bioethics (2023)

Click to increase image sizeClick to decrease image sizeThis article refers to:Ethical Responsibilities for Companies That Process Personal Data ACKNOWLEDGEMENTThe authors extend their gratitude to the members of the Health Data and Technology Advisory Board for their ongoing efforts, which supported the content and direction of this article.DISCLOSURE STATEMENTNo potential conflict of interest was reported by the author(s).Additional informationFundingThe authors’ work on the Health Data and Technology Advisory Board is jointly funded by the Mayo Clinic Platform, Center for Individualized Medicine, and Biomedical Ethics Research Program.
The Quest for Humane Termination of Intractable Suffering May Be an Uphill Struggle, Not a Downhill Slide on a Slippery Slope
Authors: Joel Yager, Thomas B. Strouse, Jonathan Treem
Journal: The American Journal of Bioethics (2023)

Click to increase image sizeClick to decrease image sizeThis article refers to:Slowing the Slide Down the Slippery Slope of Medical Assistance in Dying: Mutual Learnings for Canada and the USThis article is referred to by:Canadian Medical Assistance in Dying and the Hegemony of Privilege DISCLOSURE STATEMENTNo potential conflict of interest was reported by the author(s).Additional informationFundingThe author(s) reported there is no funding associated with the work featured in this article.
Computational Ethics Tools to Audit Corporate Self-Governance in Data Processing
Authors: Christine R. Deeney, Kristin Kostick-Quenet
Journal: The American Journal of Bioethics (2023)

Click to increase image sizeClick to decrease image sizeThis article refers to:Ethical Responsibilities for Companies That Process Personal Data DISCLOSURE STATEMENTNo potential conflict of interest was reported by the author(s).Additional informationFundingThis work was supported by National Institute for Mental Health of the National Institutes of Health under award number 3R01MH125958-02S1.
The Slippery Slope Argument and Assisted Death: Which Approach to MAiD Does It Really Support?
Authors: Perrine Galmiche, Valerie Mesnage, Marta Spranzi
Journal: The American Journal of Bioethics (2023)

Click to increase image sizeClick to decrease image sizeThis article refers to:Slowing the Slide Down the Slippery Slope of Medical Assistance in Dying: Mutual Learnings for Canada and the US ACKNOWLEDGMENTSThe authors are grateful to the members, interns and residents of the Center for Clinical ethics (AP-HP, Paris, France; https://ethique-clinique.aphp.fr/english/). Our lively and ongoing discussions about end-of-life issues, and our clinical ethics consultation experience have greatly contributed to our outlook on these issues.AUTHORS’ CONTRIBUTIONSMarta Spranzi has provided the main line of argument and structure of the paper. Perrine Galmiche and Valerie Mesnage have reviewed the relevant literature and collected the empirical data which can be brought to bear on the subject. Perrine Galmiche and Marta Spranzi have both contributed to the writing of the paper.DISCLOSURE STATEMENTNo potential conflict of interest was reported by the author(s).Notes1 Interview to the French Press on August 1st, 2023 in Le Nouvel Observateur (Available in French at: https://www.nouvelobs.com/societe/20230801.OBS76440/fin-de-vie-la-decision-devra-etre-reversible-a-tout-moment-estime-agnes-firmin-le-bodo.html; accessed August 20th, 2023)Additional informationFundingThe author(s) reported there is no funding associated with the work featured in this article.
Number of Follow-Up Years Needed to Identify a Rapid Decline in FEV<sub>1</sub>
Authors: Anders Lundquist, Anne Lindberg, Jonas Eriksson-Ström, Anders Blomberg, Helena Backman
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

"Number of Follow-Up Years Needed to Identify a Rapid Decline in FEV1." American Journal of Respiratory and Critical Care Medicine, 0(ja), pp.
Empowering Queer Data Justice
Authors: Anthony K J Smith, Allegra Schermuly, Christy E. Newman, Lisa Fitzgerald, Mark D. M. Davis
Journal: The American Journal of Bioethics (2023)

Click to increase image sizeClick to decrease image sizeThis article refers to:Ethical Responsibilities for Companies That Process Personal Data DISCLOSURE STATEMENTNo potential conflict of interest was reported by the author(s).Additional informationFundingThis publication was supported by an Australian Research Council Discovery Project Grant [DP230100245].
Comparisons Only Yield Valid Mutual Learnings If Based on Accurate Descriptions of the Comparators
Authors: Jocelyn Downie
Journal: The American Journal of Bioethics (2023)

Click to increase image sizeClick to decrease image sizeThis article refers to:Slowing the Slide Down the Slippery Slope of Medical Assistance in Dying: Mutual Learnings for Canada and the USThis article is referred to by:Canadian Medical Assistance in Dying and the Hegemony of Privilege DISCLOSURE STATEMENTThe author was a member of the plaintiffs’ legal team in Carter v. Canada.Additional informationFundingThe author(s) reported there is no funding associated with the work featured in this article.
Aid in Dying in Canada and the United States: Are U.S. States Too Cautious?
Authors: David Orentlicher
Journal: The American Journal of Bioethics (2023)

Click to increase image sizeClick to decrease image sizeThis article refers to:Slowing the Slide Down the Slippery Slope of Medical Assistance in Dying: Mutual Learnings for Canada and the US ACKNOWLEDGMENTThe author is grateful for helpful background discussion with Jocelyn Downie.DISCLOSURE STATEMENTThe author is collaborating with Compassion & Choices on an update to guidelines for clinicians providing aid-in-dying services and also worked with Compassion & Choices on a legislative proposal to legalize aid in dying in Nevada.Notes1 Pullman cites 0.15 percent for California in 2020 and 2021. In 2022, the rate was 0.3 percent, California Department of Public Health. 2023. California End of Life Option Act Report 2022 Data Report, available at https://www.cdph.ca.gov/Programs/CHSI/CDPH%20Document%20Library/CDPH_End_of_Life%20_Option_Act_Report_2022_FINAL.pdf, and in Oregon in 2022, 0.6 percent of deaths occurred via aid in dying (Oregon Health Authority Citation2023).2 Grievous and irremediable condition is defined to mean that the patient has “a serious and incurable illness, disease or disability,” is “in an advanced state of irreversible decline in capability,” and is experiencing “physical or psychological suffering that is intolerable to [the patient]” and “that cannot be relieved under conditions that [the patient] consider[s] acceptable.” Id.3 In other words, U.S. states equate terminal illness with serious and irreversible illness.4 Canadian law also tries to avoid quality of life judgments by requiring that the suffering be intolerable to the patient and unable to be relieved under conditions that the patient considers acceptable. Supra note 2.5 California Department of Public Health. 2023. California End of Life Option Act Report 2022 Data Report, available at https://www.cdph.ca.gov/Programs/CHSI/CDPH%20Document%20Library/CDPH_End_of_Life%20_Option_Act_Report_2022_FINAL.pdf.6 N.J. Stat. § 26:16-10.7 Or. Rev. Stat. § 127.840.Additional informationFundingThe author(s) reported there is no funding associated with the work featured in this article.
Of Slopes and Ropes: Learning from the Diversity of European Regulations of Assisted Dying
Authors: Ralf J. Jox
Journal: The American Journal of Bioethics (2023)

Click to increase image sizeClick to decrease image sizeThis article refers to:Slowing the Slide Down the Slippery Slope of Medical Assistance in Dying: Mutual Learnings for Canada and the US Disclosure statementNo potential conflict of interest was reported by the author(s).Additional informationFundingThe author(s) reported there is no funding associated with the work featured in this article.
Undiagnosed Alpha-1 Antitrypsin Deficiency and the Perpetuation of Lung Health Inequity
Authors: Oliver J. McElvaney, Jon Hagstrom, Marilyn G. Foreman, Noel G. McElvaney
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

"Undiagnosed Alpha-1 Antitrypsin Deficiency and the Perpetuation of Lung Health Inequity." American Journal of Respiratory and Critical Care Medicine, 0(ja), pp.
<i>EGFR</i>-Mutant NSCLC: Spotlight on Amivantamab
Journal: Cancer Discovery (2023)

Abstract Data from three phase III trials—PAPILLON, MARIPOSA, and MARIPOSA-2—highlight amivantamab, an EGFR–MET bispecific antibody, as a potential contender as a standard treatment for EGFR-mutant non–small cell lung cancer. Amivantamab paired with chemotherapy is a superior first-line option for patients with exon 20–mutated disease. Beyond this subset, compared with standard osimertinib, the combination with or without lazertinib also boosted progression-free survival, albeit at the cost of added toxicity.
Drug-Eluting Resorbable Scaffold versus Angioplasty for Infrapopliteal Artery Disease
Authors: Ramon L. Varcoe, Brian G. DeRubertis, Raghu Kolluri, Prakash Krishnan, David C. Metzger, Marc P. Bonaca, Mehdi H. Shishehbor, Andrew H. Holden, Danielle R. Bajakian, Lawrence A. Garcia, Steven W.C. Kum, John Rundback, Ehrin Armstrong, Jen-Kuang Lee, Yazan Khatib, Ido Weinberg, Hector M. Garcia-Garcia, Karine Ruster, Nutte T. Teraphongphom, Yan Zheng, Jin Wang, Jennifer M. Jones-McMeans, Sahil A. Parikh
Journal: New England Journal of Medicine (2023)

Among patients with chronic limb-threatening ischemia (CLTI) and infrapopliteal artery disease, angioplasty has been associated with frequent reintervention and adverse limb outcomes from restenosis. The effect of the use of drug-eluting resorbable scaffolds on these outcomes remains unknown. In this multicenter, randomized, controlled trial, 261 patients with CLTI and infrapopliteal artery disease were randomly assigned in a 2:1 ratio to receive treatment with an everolimus-eluting resorbable scaffold or angioplasty. The primary efficacy end point was freedom from the following events at 1 year: amputation above the ankle of the target limb, occlusion of the target vessel, clinically driven revascularization of the target lesion, and binary restenosis of the target lesion. The primary safety end point was freedom from major adverse limb events at 6 months and from perioperative death. The primary efficacy end point was observed (i.e., no events occurred) in 135 of 173 patients in the scaffold group and 48 of 88 patients in the angioplasty group (Kaplan–Meier estimate, 74% vs. 44%; absolute difference, 30 percentage points; 95% confidence interval [CI], 15 to 46; one-sided P<0.001 for superiority). The primary safety end point was observed in 165 of 170 patients in the scaffold group and 90 of 90 patients in the angioplasty group (absolute difference, −3 percentage points; 95% CI, −6 to 0; one-sided P<0.001 for noninferiority). Serious adverse events related to the index procedure occurred in 2% of the patients in the scaffold group and 3% of those in the angioplasty group. Among patients with CLTI due to infrapopliteal artery disease, the use of an everolimus-eluting resorbable scaffold was superior to angioplasty with respect to the primary efficacy end point. (Funded by Abbott; LIFE-BTK ClinicalTrials.gov number, NCT04227899.)
Differential Associations of A-/B-Type Natriuretic Peptides With Cardiac Structure, Function, and Prognosis in Heart Failure
Authors: Eugene S.J. Tan, Siew Pang Chan, Oi Wah Liew, Jenny P.C. Chong, Kui Toh Gerard Leong, Poh Shuan Daniel Yeo, Hean Yee Ong, Fazlur Jaufeerally, David Sim, Lieng Hsi Ling, Carolyn S.P. Lam, A. Mark Richards
Journal: JACC Heart Failure (2023)
Reprogramming T cell differentiation and exhaustion in CAR-T cell therapy
Authors: Yannick Bulliard, Borje S. Andersson, Mehmet A. Baysal, Jason Damiano, Apostolia M. Tsimberidou
Journal: Journal of Hematology & Oncology (2023)

Abstract T cell differentiation is a highly regulated, multi-step process necessary for the progressive establishment of effector functions, immunological memory, and long-term control of pathogens. In response to strong stimulation, as seen in severe or chronic infections or cancer, T cells acquire a state of hypo-responsiveness known as exhaustion, limiting their effector function. Recent advances in autologous chimeric antigen receptor (CAR)-T cell therapies have revolutionized the treatment of hematologic malignancies by taking advantage of the basic principles of T cell biology to engineer products that promote long-lasting T cell response. However, many patients’ malignancies remain unresponsive to treatment or are prone to recur. Discoveries in T cell biology, including the identification of key regulators of differentiation and exhaustion, offer novel opportunities to have a durable impact on the fate of CAR-T cells after infusion. Such next-generation CAR-T cell therapies and their clinical implementation may result in the next leap forward in cancer treatment for selected patients. In this context, this review summarizes the foundational principles of T cell differentiation and exhaustion and describes how they can be utilized and targeted to further improve the design and efficacy of CAR-T cell therapies.
Prognostic impact of measurable residual clonal hematopoiesis in acute myeloid leukemia patients after allogeneic hematopoietic stem cell transplantation
Authors: Lara Bischof, Jule Ussmann, Juliane Grimm, Marius Bill, Dominic Brauer, Donata Backhaus, Lisa Herrmann, Maximilian Merz, Marco Herling, Klaus H. Metzeler, Georg-Nikolaus Franke, Vladan Vucinic, Uwe Platzbecker, Sebastian Schwind, Madlen Jentzsch
Journal: Leukemia (2023)

Graphical Abstract
Right heart echocardiography findings in hypoxic pneumonia patients during the COVID-19 pandemic in a South African population
Authors: S A van Blydenstein, S Omar, B Jacobson, C N Menezes, R Meel
Journal:  (2023)

Abstract Aims The right ventricle is affected by Coronavirus disease 19 (COVID-19) via multiple mechanisms, which can result in right ventricular dysfunction (RVD). This study aimed to provide an assessment of right heart function using conventional echocardiography and advanced strain imaging, in patients with hypoxic pneumonia during the COVID-19 pandemic. Methods and results This study was an observational, prospective, single-centre study, including adults with hypoxic pneumonia, in two groups: COVID-19 pneumonia; and non-COVID-19 pneumonia. Bedside echocardiography was performed according to a pre-specified protocol and all right heart measurements were done as per standard guidelines. Right ventricular free wall strain (RVFWS) was measured using Philips® QLAB 11.0 speckle tracking software. Descriptive and comparative statistics were used to analyse data. Spearman Rank Order Correlations were used to determine the correlation between right ventricular (RV) parameters and clinical parameters. Univariate and multivariate logistic regression analyses were performed to characterize the predictors of in-hospital mortality. We enrolled 48 patients with COVID-19 pneumonia and 24 with non-COVID-19 pneumonia. COVID-19 patients were significantly older with a higher frequency of hypertension and diabetes and a trend towards a lower severity of illness score. Mean RVFWS yielded the highest estimates for the prevalence of RVD (81%), with no difference between the two pneumonia groups. Median Tricuspid Annular Plane Systolic Excursion (TAPSE) and right ventricular systolic excursion velocity (RVS’) were not significantly different between COVID-19 (TAPSE 17.2 and RVS’ 12), and non-COVID-19 pneumonia (TAPSE 17.8 and RVS’ 12.1) with P values of 0.29 and 0.86, respectively. Non-COVID-19 pneumonia patients with moderate to severe hypoxaemia (PF &amp;lt; 150) were at greater risk of an elevated RV Systolic Pressure &amp;gt;30 mmHg respiratory rate = 3.25 (CI 1.35–7.82) on admission. Troponin levels discriminated between COVID-19 survivors (6 ng/L) and non-survivors (13 ng/L), P = 0.04. The mortality rate for COVID-19 was high (27%) compared to non-COVID-19 pneumonia (12%). Conclusion Patients with COVID-19 pneumonia had a similar admission prevalence of RVD when compared to patients with non-COVID-19 pneumonia. Despite preserved traditional parameters of RV systolic function, RVFWS was diminished in both groups, and we propose that RVFWS serves as an important marker of the subclinical disease of RV.
John Launer: A doctor of the old school—a short memoir
Authors: John Launer
Journal: BMJ (2023)

We all have moments in our lives that are so unusual or become such turning points that we never forget them.One moment for me took place many years ago in Delhi.I'd taken annual leave from my job as a casualty officer and booked on a tour of Rajasthan.For some reason I couldn't fly out with the tour group, so I arrived the next day and joined them over breakfast at the hotel.I sat down next to two women in their 50s.They were to become my lifelong friends.Freda Fleischer, one of the women, was a GP in Balham in south London.Like my mother who had recently died, she was a Jewish refugee from Vienna, so I suppose it was natural that she should take me under her wing.Freda had met her partner Ruth Levin while a medical student at the Royal Free Hospital in London.Ruth was from Nuremberg